👤 Katsutoshi Mizumoto

Lymphomatoid granulomatosis (LYG) is a rare Epstein-Barr virus-driven B-cell lymphoproliferative disease that often progresses to high-grade lymphoma. We describe a case of high-grade LYG causing Pancoast syndrome, diagnosed via transbronchial biopsy after a failed incisional biopsy. Complete remission was achieved with R-CHOP (rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisolone), but 2.5 years later, the patient developed lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia (LPL/WM). Despite bendamustine-rituximab improving LPL/WM, LYG recurred, underscoring its treatment challenges. This case highlights LYG's diagnostic complexity, its potential link with other hematologic malignancies, and therapeutic limitations. Further research is needed to elucidate LYG's pathogenesis and develop effective treatments for relapsed cases. Show less

The guanine-rich stretch of single-stranded DNA (ssDNA) forms a G-quadruplex (G4) in a fraction of genic and intergenic chromosomal regions. The probability of G4 formation increases during events causing ssDNA generation, such as transcription and replication. In turn, G4 abrogates these events, leading to DNA damage. DHX36 unwinds G4-DNA in vitro and in human cells. However, its spatial correlation with G4-DNA in vivo and its role in genome maintenance remain unclear. Here, we demonstrate a connection between DHX36 and G4-DNA and its implications for genomic integrity. The nuclear localization of DHX36 overlapped with that of G4-DNA, RNA polymerase II, and a splicing-related factor. Depletion of DHX36 resulted in accumulated DNA damage, slower cell growth, and enhanced cell growth inhibition upon treatment with a G4-stabilizing compound; DHX36 expression reversed these defects. In contrast, the reversal upon expression of DHX36 mutants that could not bind G4 was imperfect. Thus, DHX36 may suppress DNA damage by promoting the clearance of G4-DNA for cell growth and survival. Our findings deepen the understanding of G4 resolution in the maintenance of genomic integrity. Show less

Persistent high concentration of glucose causes cellular stress and damage in diabetes via derangement of gene expressions. We previously reported high glucose activates hypoxia-inducible factor-1αand downstream gene expression in mesangial cells, leading to an extracellular matrix expansion in the glomeruli. A glucose-responsive transcription factor carbohydrate response element-binding protein (ChREBP) is a key mediator for such perturbation of gene regulation. To provide insight into glucose-mediated gene regulation in mesangial cells, we performed chromatin immunoprecipitation followed byDNAmicroarray analysis and identified platelet-derived growth factor-C (PDGF-C) as a novel target gene of ChREBP In streptozotocin-induced diabetic mice, glomerular cells showed a significant increase inPDGF-C expression; the ratio ofPDGF-C-positive cells to the total number glomerular cells demonstrated more than threefold increase when compared with control animals. In cultured human mesangial cells, high glucose enhanced expression ofPDGF-C protein by 1.9-fold. Knock-down of ChREBPabrogated this induction response. UpregulatedPDGF-C contributed to the production of typeIVand typeVIcollagen, possibly via an autocrine mechanism. Interestingly, urinaryPDGF-C levels in diabetic model mice were significantly elevated in a fashion similar to urinary albumin. Taken together, we hypothesize that a high glucose-mediated induction ofPDGF-C via ChREBPin mesangial cells contributes to the development of glomerular mesangial expansion in diabetes, which may provide a platform for novel predictive and therapeutic strategies for diabetic nephropathy. Show less